PROJECT SUMMARY/ABSTRACT The overall goal of this K23 mentored career development proposal is to support Dr. James Andrews? development as an independent, patient-oriented researcher studying the contribution of sarcopenia to hospital-associated physical disability among older adults. Dr. Andrews is an Acting Assistant Professor in the Division of Rheumatology at the University of Washington (UW). Conducting the activities proposed in this application will facilitate Dr. Andrews? training goals of gaining hands-on experience with geriatrics patient- oriented research on clinical outcomes of acute illness, learning advanced skills in key areas (Epidemiology/Biostatistics, body composition/sarcopenia assessment, skeletal muscle metabolism), and establishing a research program examining functional outcomes of acute illness in older adults. The proposed project builds upon Dr. Andrews? experiences studying disability in rheumatic and non-rheumatic populations and his skills in clinical outcomes research; and it leverages UW?s world-class investigators, facilities, and mentorship opportunities to allow Dr. Andrews to achieve his goal of being an independent clinical investigator. This project?s primary research objective is to test the central hypothesis that sarcopenia is a risk factor for hospital-associated activity of daily living (ADL) disability among older adults. Half of all physical disability in older adults arises in the setting of hospitalization. Aging-related sarcopenia strongly predicts long-term functional outcomes (e.g. ADL disability, death) in older adults, but the relationship between sarcopenia and hospital-associated disability is unknown. Establishing sarcopenia as a risk factor for hospital-associated disability in older adults is a critical first step in understanding pathogenesis, identifying key effect modifiers and the most at-risk individuals, and ultimately developing novel interventions to prevent hospital-associated disability for the approximately 50 million older adults hospitalized each year in the United States. Aim 1 leverages the NIA-funded Health ABC dataset to identify sarcopenia (lean muscle mass and grip strength) as a risk factor for hospital-associated ADL disability among adults aged ? 70 years. Aim 2 & 3 will develop an original cohort of older adults hospitalized with sepsis to identify 1.) lean mass and grip strength and 2.) serum measures of skeletal muscle metabolism as predictors of hospital-associated ADL outcomes. The proposed aims will be among the first to examine aging-related sarcopenia as a risk factor for hospital-associated ADL disability in older adults and to expose mechanism of skeletal muscle metabolism with therapeutic potential. Combined with an outstanding mentorship team and a rigorous training plan, this project will prepare Dr. Andrews? to successfully obtain R01 funding to test novel sarcopenia-targeted interventions to prevent hospital-associated ADL disability among older adults.